Skip to main content
SpringerLink
Log in

Development of bacteriochlorophyll a-based near-infrared photosensitizers conjugated to gold nanoparticles for photodynamic therapy of cancer

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

We report the synthesis and characterization of a new sulfur-containing derivative of bacteriochlorophyll a. The latter was isolated from biomass of the nonsulfur purple bacterium Rhodobacter capsulatus strain B10. The developed photosensitizer is N-aminobacteriopurpurinimide with an exocyclic amino group acylated with a lipoic acid moiety, which is a biogenic substance that acts as a cofactor of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes in the body. The disulfide moiety of lipoic acid confers the compound aurophilicity, thus allowing its conjugation with gold nanoparticles (NP-Au) via S—Au bonds. The shape and the size of the resulting nanoconjugate with immobilized photosensitizer (PS—Au) were assessed by dynamic light scattering and transmission electron microscopy. The conjugated nanoparticles are spherical with hydrodynamic diameter of 100–110 nm. The PS—Au conjugate absorbs light at 824 nm and emits strong fluorescence at 830 nm, which allowed in vivo study of its dynamic biodistribution in rats bearing sarcoma M-1. Compared to the free photosensitizer, PS loaded on the gold nanoparticles (PS—Au) showed extended circulation time in the blood and enhanced tumor uptake due to nonspecific passive targeting when the drug accumulates in tumor sites through the leaky tumor neovasculature and does not return to the circulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BChl a :

bacteriochlorophyll a

DLS:

dynamic light scattering

NP-Au:

gold nanoparticles

PDT:

photodynamic therapy

PS:

photosensitizer

PS—Au:

gold nanoparticles with immobilized photosensitizer

References

  1. Bonnett, R. (1999) Photodynamic therapy in historical perspective, Rev. Contemp. Pharmacother., 10, 1–17.

    CAS  Google Scholar 

  2. Dougherty, T. J., Gomer, C. J., Henderson, B. W., Jori, G., Kessel, D., Korbelik, M., Moan, J., and Peng, Q. (1998) Photodynamic therapy, J. Natl. Cancer Inst., 90, 889–905.

    Article  CAS  PubMed  Google Scholar 

  3. Stranadko, E. F. (2002) Historical development of photodynamic therapy, Lazer. Med., 4, 4–8.

    Google Scholar 

  4. Ronn, A. M. (1999) Pharmacokinetics in photodynamic therapy, Rev. Contemp. Pharmacother., 10, 39–46.

    CAS  Google Scholar 

  5. Freitas, I. (1990) Lipid accumulation: the common feature to photosensitizer retaining normal and malignant tissues, J. Photochem. Photobiol. B, 7, 359–361.

    Article  CAS  PubMed  Google Scholar 

  6. Mason, M. D. (1999) Cellular aspects of photodynamic therapy for cancer, Rev. Contemp. Pharmacother., 10, 25–37.

    CAS  Google Scholar 

  7. Vrouenraets, M. B., Visser, G. W., Snow, G. B., and van Dongen, G. A. (2003) Basic principles, applications in oncology and improved selectivity of photodynamic therapy, Anticancer Res., 23, 505–522.

    CAS  PubMed  Google Scholar 

  8. Allison, R. R., Downie, G. H., Cuenca, R., Hu, X. H., Childs, C. J. H., and Sibata, C. H. (2004) Photosensitizers in clinical PDT, Photodiagn. Photodyn. Ther., 1, 27–42.

    Article  CAS  Google Scholar 

  9. Moan, J., Peng, Q., Iani, V., Ma, L. W., Horobin, R. W., Berg, K., Kongshaug, M., and Nesland, J. M. (1995) Biodistribution, pharmacokinetic and in vivo fluorescence spectroscopic studies of photosensitizers, SPIE, 2625, 234–238.

    Google Scholar 

  10. Moser, J. G. (1997) Definitions and general properties of 2nd and 3rd generation photosensitizers, in Photodynamic Tumor Therapy, 2nd and 3rd Generation Photosensitizers (Moser, J. G., ed.) Harwood Academic Publishers, London, pp. 3–8.

    Google Scholar 

  11. Henderson, B. W., Sumlin, A. B., Owcharczak, B. L., and Dougherty, T. J. (1991) Bacteriochlorophyll a as photosensitizer for photodynamic treatment of transplantable murine tumors, Photochem. Photobiol. B, 10, 303–313.

    Article  CAS  Google Scholar 

  12. Koudinova, N. V., Pinthus, J. H., Brandis, A., Brenner, O., Bendel, P., Ramon, J., Eshhar, Z., Scherz, A., and Salomon, Y. (2003) Photodynamic therapy with Pd-bacteriopheophorbide (TOOKAD): successful in vivo treatment of human prostatic small cell carcinoma xenografts, Int. J. Cancer, 104, 782–789.

    Article  CAS  PubMed  Google Scholar 

  13. Brandis, A., Mazor, O., Neumark, E., Rozenbach-Belkin, V., Salomon, Y., and Scherz, A. (2005) Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: synthesis, solubility, phototoxicity and the effect of serum proteins, Photochem. Photobiol., 81, 983–993.

    Article  CAS  PubMed  Google Scholar 

  14. Grin, M. A., Mironov, A. F., and Shtil, A. A. (2008) Bacteriochlorophyll a and its derivatives: chemistry and perspectives for cancer therapy, Anti-cancer Agents Med. Chem., 8, 683–697.

    Article  CAS  Google Scholar 

  15. Mironov, A. F., and Grin, M. A. (2008) Synthesis of chlorin and bacteriochlorin conjugates for photodynamic and boron neutron capture therapy, J. Porphyrins Phthalocyanines, 12, 1163–1172.

    Article  CAS  Google Scholar 

  16. Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., and Langer, R. (2007) Nano-carriers as an emerging platform for cancer therapy, Nat. Nanotech., 2, 751–760.

    Article  CAS  Google Scholar 

  17. Ghosh, P., Han, G., De, M., Kim, C. K., and Rotello, V. M. (2008) Gold nanoparticles in delivery applications, Adv. Drug Delivery Rev., 60, 1307–1315.

    Article  CAS  Google Scholar 

  18. Rana, S., Bajaj, A., Mout, R., and Rotello, V. M. (2012) Monolayer coated gold nanoparticles for delivery applications, Adv. Drug Delivery Rev., 64, 200–216.

    Article  CAS  Google Scholar 

  19. Dreaden, E. C., Alkilany, A. M., Huang, X., Murphy, C. J., and El-Sayed, M. A. (2012) The golden age: gold nanoparticles for biomedicine, Chem. Soc. Rev., 41, 2740–2779.

    Article  CAS  PubMed  Google Scholar 

  20. Bardhan, R., Lal, S., Joshi, A., and Halas, N. J. (2011) Theranostic nano-shells: from probe design to imaging and treatment of cancer, Acc. Chem. Res., 44, 936–946.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Xia, Y., Li, W., Cobley, C. M., Chen, J., Xia, X., Zhang, Q., Yang, M., Cho, E. C., and Brown, P. K. (2011) Gold nanocages: from synthesis to theranostic applications, Acc. Chem. Res., 44, 914–924.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Cheng, Y. C., Samia, A., Meyers, J. D., Panagopoulos, I., Fei, B., and Burda, C. (2008) Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer, J. Am. Chem. Soc., 130, 10643–10647.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Cheng, Y., Samia, A. C., Li, J., Kenney, M. E., Resnick, A., and Burda, C. (2009) Delivery and efficacy of a cancer drug as a function of the bond to the gold nanoparticle surface, Langmuir, 26, 2248–2255.

    Article  Google Scholar 

  24. Cheng, Y., Meyers, J. D., Broome, A.-M., Kenney, M. E., Basilion, J. P., and Burda, C. (2011) Deep penetration of a PDT drug into tumors by noncovalent drug-gold nanoparticle conjugates, J. Am. Chem. Soc., 133, 2583–2591.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Srivatsan, A., Jenkins, S. V., Jeon, M., Wu, Z., Kim, C., Chen, J., and Pandey, R. K. (2014) Gold nanocage-photosensitizer conjugates for dual-modal image-guided enhanced photodynamic therapy, Theranostics, 4, 163–174.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Mieszawska, A. J., Mulder, W. J. M., Fayad, Z. A., and Cormode, D. P. (2013) Multifunctional gold nanoparticles for diagnosis and therapy of disease, Mol. Pharm., 10, 831–847.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Galper, M. W., Saung, M. T., Fuster, V., Roessl, E., Thran, A., Proksa, R., Fayad, Z. A., and Cormode, D. P. (2012) Effect of computed tomography scanning parameters on gold nanoparticle and iodine contrast, Invest. Radiol., 47, 475–481.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Liu, C. J., Wang, C. H., Chen, S. T., Chen, H. H., Leng, W. H., Chien, C. C., Wang, C. L., Kempson, I. M., Hwu, Y., Lai, T. C., Hsiao, M., Yang, C. S., Chen, Y. J., and Margaritondo, G. (2010) Enhancement of cell radiation sensitivity by pegylated gold nanoparticles, Phys. Med. Biol., 55, 931–945.

    Article  CAS  PubMed  Google Scholar 

  29. Chen, X., Chen, Y., Yan, M., and Qiu, M. (2012) Nanosecond photothermal effects in plasmonic nanostructures, ACS Nano, 6, 2550–2557.

    Article  CAS  PubMed  Google Scholar 

  30. Chen, H., Shao, L., Ming, T., Sun, Z., Zhao, C., Yang, B., and Wang, J. (2010) Understanding the photothermal conversion efficiency of gold nanocrystals, Small, 6, 2272–2280.

    Article  CAS  PubMed  Google Scholar 

  31. Huang, X., Kang, B., Qian, W., Mackey, M. A., Chen, P. C., Oyelere, A. K., El-Sayed, I. H., and El-Sayed, M. A. (2010) Comparative study of photothermolysis of cancer cells with nuclear-targeted or cytoplasm-targeted gold nanospheres: continuous wave or pulsed lasers, J. Biomed. Opt., 15, 0580–2.

    Google Scholar 

  32. Mironov, A. F., Kozyrev, A. N., and Brandis, A. S. (1992) Sensitizers of second generation for photodynamic therapy of cancer based on chlorophyll and bacteriochlorophyll derivatives, Proc. SPIE, 1922, 204–208.

    Google Scholar 

  33. Mironov, A. F., Grin, M. A., Tsiprovskiy, A. G., Dzardanov, D. V., Golovin, K. V., Feofanov, A. V., and Yakubovskaya, R. I. (2004) Bacteriochlorophyll a-based hydrazides possessing photodynamic activity and method for their preparation, Patent RF 2223274 [in Russian].

    Google Scholar 

  34. Mironov, A. F., Grin, M. A., Tsiprovskiy, A. G., Kachala, V. V., Karmakova, T. A., Plyutinskaya, A. D., and Yakubovskaya, R. I. (2003) New bacteriochlorin derivatives with a fused N-aminoimide ring, J. Porphyrins Phthalocyanines, 7, 725–730.

    Article  CAS  Google Scholar 

  35. Mironov, A. F., and Efremov, A. V. (1996) Synthesis of bacteriochlorophyll a, Patent RF 2144085 [in Russian].

    Google Scholar 

  36. Tsygankov, A. A., Laurinavichene, T. V., and Gogotov, I. N. (1994) Laboratory scale photobioreactor, Biotechnol. Tech., 8, 575–578.

    Article  CAS  Google Scholar 

  37. Tsygankov, A. A., Laurinavichene, T. V., Bukatin, V. E., Gogotov, I. N., and Hall, D. O. (1997) Biomass production by continuous cultures of Rhodobacter capsulatus grown in various bioreactors, Biochem. Microbiol., 33, 485–490.

    Google Scholar 

  38. Patrusheva, E. V., Fedorov, A. C., Belera, V. V., Minkevich, I. G., and Tsygankov, A. A. (2007) Synthesis of bacteriochlorophyll a by the purple nonsulfur bacterium Rhodobacter capsulatus, Appl. Biochem. Microbiol., 43, 187–192.

    Article  CAS  Google Scholar 

  39. Sharonov, G. V., Karmakova, T. A., Kassies, R., Pljutinskaya, A. D., Refregiers, M., Yakubovskaya, R. I., Mironov, A. F., Grin, M. A., Maurizot, J.-C., Vigny, P., Otto, C., and Feofanov, A. V. (2006) Cycloimide bacteriochlorin p derivatives: photodynamic properties, cellular and tissue distribution, Free Radicals Biol. Med., 40, 407–419.

    Article  CAS  Google Scholar 

  40. Turkevich, J., Stevenson, P. C., and Hillier, J. (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold, Discuss. Faraday Soc., 11, 55–75.

    Article  Google Scholar 

  41. Frens, G. (1973) Controlled nucleation for regulation of particle size in monodisperse gold suspensions, Nat. Phys. Sci., 241, 20–22.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lomonosov Moscow State University of Fine Chemical Technologies, 119571, Moscow, Russia

    I. V. Pantiushenko, M. A. Grin & A. F. Mironov

  2. Lomonosov Moscow State University, 119991, Moscow, Russia

    P. G. Rudakovskaya & A. G. Majouga

  3. National University of Science and Technology MISiS, 119991, Moscow, Russia

    P. G. Rudakovskaya & A. G. Majouga

  4. Cyb Scientific Research Center of Radiology, Hertsen Federal Medical Research Center, Ministry of Health of the Russian Federation, 249036, Obninsk, Kaluga Region, Russia

    A. V. Starovoytova, A. A. Mikhaylovskaya & M. A. Kaplan

  5. Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    M. A. Abakumov

  6. Institute of Basic Biological Problems, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    A. A. Tsygankov

Authors
  1. I. V. Pantiushenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. G. Rudakovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. V. Starovoytova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. A. Mikhaylovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. A. Abakumov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. A. Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. A. Tsygankov
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. G. Majouga
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. A. Grin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. F. Mironov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. A. Grin.

Additional information

Original Russian Text © I. V. Pantiushenko, P. G. Rudakovskaya, A. V. Starovoytova, A. A. Mikhaylovskaya, M. A. Abakumov, M. A. Kaplan, A. A. Tsygankov, A. G. Majouga, M. A. Grin, A. F. Mironov, 2015, published in Biokhimiya, 2015, Vol. 80, No. 6, pp. 891–902.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pantiushenko, I.V., Rudakovskaya, P.G., Starovoytova, A.V. et al. Development of bacteriochlorophyll a-based near-infrared photosensitizers conjugated to gold nanoparticles for photodynamic therapy of cancer. Biochemistry Moscow 80, 752–762 (2015). https://doi.org/10.1134/S0006297915060103

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297915060103

Key words

Search

Navigation